洞察三角叶马兰（Jacq.）水提物中具有抗氧化样活性的已鉴定生物活性化合物，并通过计算方法探索其作为潜在乙酰胆碱酯酶抑制剂的特性。

Insight into antioxidant-like activity and computational exploration of identified bioactive compounds in Talinum triangulare (Jacq.) aqueous extract as potential cholinesterase inhibitors.

机构信息

Department of Chemical Sciences, Phytomedicine and Toxicology Unit, College of Sciences, Biochemistry ProgrammeAfe-Babalola University, P.M.B 5454, Ado- Ekiti, Ekiti State, Nigeria.

Department of Medical Biochemistry, College of Medicine and Health Sciences, Afe Babalola University, P.M.B 5454, Ado-Ekiti, Ekiti State, Nigeria.

出版信息

BMC Complement Med Ther. 2024 Mar 28;24(1):134. doi: 10.1186/s12906-024-04424-2.

BACKGROUND

Recent reports have highlighted the significance of plant bioactive components in drug development targeting neurodegenerative disorders such as Alzheimer's disease (AD). Thus, the current study assessed antioxidant activity and enzyme inhibitory activity of the aqueous extract of Talinum triangulare leave (AETt) as well as molecular docking/simulation of the identified phytonutrients against human cholinesterase activities.

METHODS

In vitro assays were carried out to assess the 2,2- azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) cation radicals and cholinesterase inhibitory activities of AETt using standard protocols. High performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was employed to identify compounds in AETt. Also, for computational analysis, identified bioactive compounds from AETt were docked using Schrodinger's GLIDE against human cholinesterase obtained from the protein data bank ( https://www.rcsb.org/ ).

RESULTS

The results revealed that AETt exhibited a significant concentration-dependent inhibition against ABTS cation radicals (IC50 = 308.26 ± 4.36 µg/ml) with butylated hydroxytoluene (BHT) as the reference. Similarly, AETt demonstrated a significant inhibition against acetylcholinesterase (AChE, IC50 = 326.49 ± 2.01 µg/ml) and butyrylcholinesterase (BChE, IC50 = 219.86 ± 4.13 µg/ml) activities with galanthamine as the control. Molecular docking and simulation analyses revealed rutin and quercetin as potential hits from AETt, having showed strong binding energies for both the AChE and BChE. In addition, these findings were substantiated by analyses, including radius of gyration, root mean square fluctuation, root mean square deviation, as well as mode similarity and principal component analyses.

CONCLUSION

Overall, this study offers valuable insights into the interactions and dynamics of protein-ligand complexes, offering a basis for further drug development targeting these proteins in AD.

背景

最近的报告强调了植物生物活性成分在针对神经退行性疾病（如阿尔茨海默病）的药物开发中的重要性。因此，本研究评估了 Talinum triangulare 叶的水提物（AETt）的抗氧化活性和酶抑制活性，以及鉴定的植物营养素对人胆碱酯酶活性的分子对接/模拟。

方法

采用标准方法进行体外测定，以评估 AETt 的 2,2-氮杂双（3-乙基苯并噻唑啉-6-磺酸）（ABTS）阳离子自由基和胆碱酯酶抑制活性。采用高效液相色谱-二极管阵列检测（HPLC-DAD）鉴定 AETt 中的化合物。此外，对于计算分析，从 AETt 中鉴定出的生物活性化合物使用 Schrodinger 的 GLIDE 对接，针对从蛋白质数据库（https://www.rcsb.org/）获得的人胆碱酯酶。

结果

结果表明，AETt 对 ABTS 阳离子自由基表现出显著的浓度依赖性抑制作用（IC50=308.26±4.36μg/ml），以丁基化羟基甲苯（BHT）为参考。同样，AETt 对乙酰胆碱酯酶（AChE，IC50=326.49±2.01μg/ml）和丁酰胆碱酯酶（BChE，IC50=219.86±4.13μg/ml）活性也有显著抑制作用，以加兰他敏为对照。分子对接和模拟分析表明，芦丁和槲皮素是 AETt 的潜在有效成分，对 AChE 和 BChE 均表现出较强的结合能。此外，这些发现通过分析得到了证实，包括旋转半径、均方根波动、均方根偏差，以及模式相似性和主成分分析。